Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in NAc and PFC.

Autor: Vornholt E; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.; Integrative Life Sciences Doctoral Program, Virginia Commonwealth University, Richmond, Virginia, United States of America., Drake J; Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, Texas, United States of America., Mamdani M; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America., McMichael G; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America., Taylor ZN; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America., Bacanu SA; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.; Department Psychiatry, Virginia Commonwealth University, Richmond, Virginia, United States of America., Miles MF; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.; VCU-Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, United States of America.; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, United States of America.; Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, United States of America., Vladimirov VI; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.; Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, Texas, United States of America.; Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, Virginia, United States of America.; Department of Physiology & Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.; School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, United States of America.; Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Dec 17; Vol. 15 (12), pp. e0243857. Date of Electronic Publication: 2020 Dec 17 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0243857
Abstrakt: Chronic alcohol abuse has been linked to the disruption of executive function and allostatic conditioning of reward response dysregulation in the mesocorticolimbic pathway (MCL). Here, we analyzed genome-wide mRNA and miRNA expression from matched cases with alcohol dependence (AD) and controls (n = 35) via gene network analysis to identify unique and shared biological processes dysregulated in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We further investigated potential mRNA/miRNA interactions at the network and individual gene expression levels to identify the neurobiological mechanisms underlying AD in the brain. By using genotyped and imputed SNP data, we identified expression quantitative trait loci (eQTL) uncovering potential genetic regulatory elements for gene networks associated with AD. At a Bonferroni corrected p≤0.05, we identified significant mRNA (NAc = 6; PFC = 3) and miRNA (NAc = 3; PFC = 2) AD modules. The gene-set enrichment analyses revealed modules preserved between PFC and NAc to be enriched for immune response processes, whereas genes involved in cellular morphogenesis/localization and cilia-based cell projection were enriched in NAc modules only. At a Bonferroni corrected p≤0.05, we identified significant mRNA/miRNA network module correlations (NAc = 6; PFC = 4), which at an individual transcript level implicated miR-449a/b as potential regulators for cellular morphogenesis/localization in NAc. Finally, we identified eQTLs (NAc: mRNA = 37, miRNA = 9; PFC: mRNA = 17, miRNA = 16) which potentially mediate alcohol's effect in a brain region-specific manner. Our study highlights the neurotoxic effects of chronic alcohol abuse as well as brain region specific molecular changes that may impact the development of alcohol addiction.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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